Evaluating the quantity and spatial density of macrophage-like cells in patients with retinal vascular disease and healthy subjects via non-invasive retinal imaging.

OBJECTIVE: Here we investigate the spatial density and distribution of macrophage-like cells (MLCs) in ischemic retinal diseases, including branch retinal vein occlusion (BRVO), central retinal vein occlusion (CRVO), and proliferative diabetic retinopathy (PDR), compared to healthy controls. METHODS: In this pilot investigation with prospective cross-sectional design, OCT angiography (OCTA) images were obtained from 20 eyes across four groups (BRVO, CRVO, PDR, controls). Using a standardized semi-automated image processing protocol, MLCs were identified and quantified over a 6 × 6 mm area temporal to the macula. Additionally, perfusion densities were measured, and analyses were performed to assess differences in MLC counts and their correlations with perfusion. RESULTS: Patients with BRVO, CRVO, and PDR exhibited significantly higher MLC counts compared to controls (p = 0.002 for all comparisons). Median MLC counts were lowest in controls (132; 95% CI, 63–180), followed by BRVO (382; 95% CI, 290–446), CRVO (688; 95% CI, 507–716), and highest in PDR patients (973; 95% CI, 805–999). A moderate-to-strong negative correlation was found between perfusion density and MLC count, suggesting increased MLC accumulation in areas of reduced perfusion in the superior vascular complex (p = 0.04), deep vascular complex (p < 0.01), as well as combined vascular complexes (p = 0.01). CONCLUSION: Here, we demonstrate that MLC density is significantly elevated in BRVO, CRVO, and PDR compared to healthy eyes and is inversely correlated with retinal perfusion. By applying consistent imaging and analysis across a wider peripheral retinal field, these findings highlight MLC quantification as a potential biomarker for disease severity and progression in ischemic retinopathies. Future investigations should explore whether modulating MLC responses could offer new therapeutic strategies to improve outcomes in these conditions.